Antileishmanial activity of a 4-hydrazinoquinoline derivative: Induction of autophagy and apoptosis-related processes and effectiveness in experimental cutaneous leishmaniasis
| Autor: | Luciana M.R. Antinarelli, Wallace Pacienza Lima, Jacy Gameiro, Priscila V. S. Z. Capriles, Isabela O. Souza, Elaine Soares Coimbra, Adilson David da Silva, Celso Vataru Nakamura, Elizandra Aparecida Britta |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Leishmania mexicana 030106 microbiology Immunology Antiprotozoal Agents Leishmaniasis Cutaneous Apoptosis Vacuole Pharmacology Biology Kidney Inhibitory Concentration 50 Mice 03 medical and health sciences chemistry.chemical_compound Cutaneous leishmaniasis In vivo Chlorocebus aethiops Autophagy medicine Animals Ear External Vero Cells Mice Inbred BALB C Cell Cycle General Medicine Phosphatidylserine Cell cycle medicine.disease Leishmania biology.organism_classification Infectious Diseases Liver chemistry Creatinine Aminoquinolines Female Parasitology |
| Zdroj: | Experimental Parasitology. 195:78-86 |
| ISSN: | 0014-4894 |
| DOI: | 10.1016/j.exppara.2018.10.007 |
| Popis: | Currently, available treatment options for leishmaniasis are limited and unsatisfactory. In a previous study, a quinoline derivative (AMQ-j), exhibited a strong effect against Leishmania amazonensis and its antileishmanial activity was preliminarily associated with mitochondrial dysfunction. The present study further explores the antileishmanial effect of this compound against L. amazonensis, as well as determines the main cellular processes involved in the death of the parasite. Moreover, this study evaluated the in vivo effect of the AMQ-j in BALB/c mice experimentally infected by L. amazonensis. The results showed that the compound AMQ-j induces a set of morphological and biochemical features that could correlate with both autophagy-related and apoptosis-like processes, indicating intense mitochondrial swelling, a collapse of the mitochondrial membrane potential, an abnormal chromatin condensation, an externalization of phosphatidylserine, an accumulation of lipid bodies, a disorganization of cell cycle, a formation of autophagic vacuoles, and an increase of acidic compartments. Treatment with AMQ-j through an intralesional route was effective in reducing the parasite burden and size of the lesion. No significant increase in the serum levels of hepatic or renal damage toxicity markers was observed. These findings contribute to the understanding of the mode of action of quinoline derivatives involved in the death of Leishmania parasites and encourage new studies in other experimental models of Leishmania infection. |
| Databáze: | OpenAIRE |
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